This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. M2 is a 97 residue protein with a single transmembrane (TM) alpha helical stretch. M2 homotetramerizes to form a proton selective channel in a membrane environment. The transmembrane section (M2tm) is a 25 amino acid peptide of the sequence SSDPLVVAASIIGILHLILWILDRL. The ion channel activity of the influenza virus M2 integral membrane protein plays an important role in the life cycle of the virus. It has been proposed that Trp 41 in each one of the four transmembrane helices is crucial for the pH-gated proton channel of M2. It was found that mutation of teh His (H) in the transmembrane sequence leads to a loss of the proton selectivity and mutation of the Trp (W) amino acid allows for the outflow of protons. Thus, the goal of this project is to use fluorescence correlation spectroscopy in conjunction with excited state electron transfer (between Trp and a labeled dye probe) to probe the conformational dynamics of the indole rings as a function of pH. The information thus obtained should allow us to gain a better understanding of the proton gating mechanism of the M2 channel. We also would like to investigate the action of the small molecules Amantadine and Rimantadine which were found to block the ion channel.